|By Marketwire .||
|November 5, 2012 05:30 PM EST||
LOS ANGELES, CA -- (Marketwire) -- 11/05/12 -- The Medicines Company (NASDAQ: MDCO) announced today the first presentation of PRONTO, a study of emergency patients with acute heart failure associated with high blood pressure enrolled within hours of their hospital arrival, making it the earliest examination of acute heart failure treatment ever performed in a clinical trial. More than 1 million acute heart failure patients each year present -- mainly to emergency departments -- at US hospitals. About half of these have high blood pressure.
The primary objective and the main secondary objective of the PRONTO clinical trial were met. Patients randomized to early treatment with Cleviprex® (clevidipine) Injectable Emulsion demonstrated more rapid and greater blood pressure reductions (p-value < 0.001). Patients reported that shortness of breath, their most distressing symptom, resolved more rapidly than with the current standard of care (SOC) (overall p-value 0.037). Safety measures were similar for both randomized treatments.
These findings were presented by W. Frank Peacock IV, MD, FACEP, Emergency Medicine Research Director at Baylor College of Medicine and Principal Investigator for PRONTO on behalf of a group of leading international acute heart failure investigators and discussed during the "Clevidipine Improves Dyspnea in Emergency Department Acute Heart Failure: A Randomized, Open Label Study" presentation (abstract 15606), presented today at the American Heart Association Scientific Sessions 2012 in Los Angeles, California.
PRONTO Purpose and Potential Implications
Dr. Peacock discussed why he is particularly excited about the data: "PRONTO was the first major heart failure trial in the last decade that displayed a significant improvement in dyspnea vs. SOC." Dr. Peacock added, "Dyspnea is the number one reason heart failure patients go to the hospital and stay there. An agent that can relieve dyspnea may have the potential to decrease associated length of stay and hospital costs as well as improve the quality of life for patients. The faster we can improve their breathing, the sooner they can go home." Of the more than 1 million patients admitted to hospitals for heart failure each year, the mean length of stay is nearly 5 days. The costs associated with these patients' hospitalizations is estimated at approximately $40 billion annually in the US.1
Gregg C. Fonarow, MD, FACC, Professor of Medicine, Ahmanson-UCLA Cardiomyopathy Center Director, UCLA Division of Cardiology Co-Chief and PRONTO Steering Committee member, noted potentially important clinical implications in the PRONTO data: "According to the findings, clevidipine treated dyspnea better than established standard of care therapies. This challenges previously held paradigms that calcium channel antagonists should be avoided in patients with acute heart failure. Further trials are needed to corroborate these findings, but clevidipine may provide an attractive treatment option to reduce blood pressure and improve breathing for acute heart failure patients who are hypertensive."
PRONTO Study Methods, Results and Limitations
A randomized open-label, multi-center trial, PRONTO (A Safety and Efficacy Study of Blood Pressure Control in Acute Heart Failure -- A Pilot Study), enrolled 104 emergency department hypertensive acute heart failure patients who exhibited pulmonary congestion. After setting a 30-minute target systolic blood pressure (SBP) range, patients were randomly treated with clevidipine or SOC (predominantly nitroglycerin and nicardipine), each administered per approved labeling.
In this trial, clevidipine met the composite primary endpoint of median time and percent of patients to reach target SBP range and a 15% blood pressure reduction in the first 30 minutes of therapy. Approximately twice as many clevidipine-treated patients achieved this endpoint than SOC-treated patients (70.5 vs. 36.6%). The median time to achieve this endpoint for clevidipine-treated patients was 15 minutes. The median time for SOC treated patients could not be estimated because fewer than 50% of patients achieved the primary endpoint (p=0.0006). The SOC-treated patients that achieved this endpoint did so in a median of 18 minutes.
In addition, clevidipine met the main secondary endpoint: dyspnea reduction (improved breathing). Within 45 minutes, the dyspnea visual analogue scale (VAS) for shortness of breath decreased more from baseline with clevidipine (median -3.6 cm) than with SOC (-2.1 cm), p=0.012. This effect was maintained to 3 hours with overall effect (p=0.037).
The percentage of patients with at least one study drug related treatment-emergent adverse event was similar in the clevidipine (9.8%) and SOC (13.2%) groups. The most common of these events was headache.
Limitations of the trial included its relatively small sample size, powered for the primary but not for all secondary endpoints, and the open label design, which makes subjective dyspnea assessments challenging. The standard of care (SOC) treatment comparator -- while representative of real care -- may have provided an inconsistent control group, although subset analysis did not suggest such confounding.
About Cleviprex® (clevidipine) Injectable Emulsion
Cleviprex (clevidipine) is an intravenous dihydropyridine calcium channel blocker indicated for the reduction of blood pressure when oral therapy is not feasible or not desirable. In June 2011, the U.S. Food and Drug Administration (FDA) approved the current formulation, which triples the maximum allowable infusion time per vial, commonly referred to in hospitals as "hang time," to 12 hours compared to the original 4-hour hang time vial approved by the FDA in 2008.
Important Safety Information About Cleviprex (clevidipine)
Cleviprex (clevidipine) is contraindicated in patients with allergies to soybeans, soy products, eggs or egg products; defective lipid metabolism seen in conditions such as pathologic hyperlipemia, lipoid nephrosis or acute pancreatitis if it is accompanied by hyperlipidemia; and severe aortic stenosis.
Cleviprex is intended for intravenous use. Use aseptic technique and discard any unused product within 12 hours of stopper puncture.
Hypotension and reflex tachycardia are potential consequences of rapid upward titration of Cleviprex. If either occurs, decrease the dose of Cleviprex. There is limited experience with short-duration therapy with beta-blockers as a treatment for Cleviprex-induced tachycardia. Beta-blocker use for this purpose is not recommended.
Cleviprex contains approximately 0.2 g of lipid per mL (2.0 kcal). Lipid intake restrictions may be necessary for patients with significant disorders of lipid metabolism.
Dihydropyridine calcium channel blockers can produce negative inotropic effects and exacerbate heart failure. Monitor heart failure patients carefully.
Cleviprex is not a beta-blocker, does not reduce heart rate and gives no protection against the effects of abrupt beta-blocker withdrawal. Beta-blockers should be withdrawn only after a gradual reduction in dose.
Patients who receive prolonged Cleviprex infusions and are not transitioned to other antihypertensive therapies should be monitored for the possibility of rebound hypertension for at least 8 hours after the infusion is stopped.
There is no information to guide use of Cleviprex in treating hypertension associated with pheochromocytoma.
Most common adverse reactions are ( > 2%) headache, nausea, and vomiting.
About The Medicines Company
The Medicines Company (NASDAQ: MDCO) provides medical solutions to improve health outcomes for patients in acute and intensive care hospitals worldwide. These solutions comprise medicines and knowledge that directly impact the survival and well being of critically ill patients. The Medicines Company's website is www.themedicinescompany.com.
Statements contained in this press release about The Medicines Company that are not purely historical, and all other statements that are not purely historical, may be deemed to be forward-looking statements for purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words "believes," "anticipates" and "expects" and similar expressions, including the Company's preliminary revenue results, are intended to identify forward-looking statements. These forward-looking statements involve known and unknown risks and uncertainties that may cause the Company's actual results, levels of activity, performance or achievements to be materially different from those expressed or implied by these forward-looking statements. Important factors that may cause or contribute to such differences include the extent of the commercial success of Angiomax, the Company's ability to develop its global operations and penetrate foreign markets, whether the Company's products will advance in the clinical trials process on a timely basis or at all, whether the Company will make regulatory submissions for product candidates on a timely basis, whether its regulatory submissions will receive approvals from regulatory agencies on a timely basis or at all, whether physicians, patients and other key decision makers will accept clinical trial results, risks associated with the establishment of international operations, and such other factors as are set forth in the risk factors detailed from time to time in the Company's periodic reports and registration statements filed with the Securities and Exchange Commission including, without limitation, the risk factors detailed in the Company's Quarterly Report on Form 10-Q filed on August 9, 2012, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.
1. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics - 2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2-e220.
The Medicines Company